Renin-synthesizing cells are known to be crucial in the regulation of blood pressure and fluid and electrolyte homeostasis. These cells have been considered as terminally differentiated because they synthesize a hormone (renin), are few in numbers, and are restricted to a juxtaglomerular localization in the adult mammalian kidney. Recently, however, we showed that renin cells are precursors for multiple renal and extrarenal cell types. Although it has been accepted that renin cells derive from the mesoderm, our preliminary work indicates that either a subset or all of the renin-expressing cells may derive from ectoderm. We further hypothesize that renin is necessary for the differentiation of ectodermal precursors into their derivative tissues (i.e. skin, choroid plexus, sympathetic ganglia, adrenal medulla and head cartilage). To define whether renin-expressing cells derive from neuroectodermal or neural crest cells we will use available mouse models that mark cells derived from the neuroectoderm, the neural crest and the renin cell lineage. To determine whether deletion of the renin gene in neuroectodermal/neural crest/ epidermal precursors results in defective development of their derivative tissues, we will generate a renin-floxed mouse and will cross it with mice expressing ere recombinase in precursors of neuroectoderm (nestin-cre), neural crest cells (wnt1-cre) and epidermis (K14-cre). The proposed studies should generate fundamental new knowledge on renin cell specification and neural/ectodermal development. Furthermore, the generation of a renin-floxed mouse will be a valuable tool to solve the long standing controversy regarding the role of locally generated renin versus circulating renin. This work has the potential to open new avenues for the understanding, prevention and treatment of hypertension, birth defects and kidney diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK075481-04
Application #
7638487
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2006-09-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$124,713
Indirect Cost
Name
University of Virginia
Department
Pediatrics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Castellanos-Rivera, Ruth M; Pentz, Ellen S; Lin, Eugene et al. (2015) Recombination signal binding protein for Ig-?J region regulates juxtaglomerular cell phenotype by activating the myo-endocrine program and suppressing ectopic gene expression. J Am Soc Nephrol 26:67-80
Pentz, Ellen Steward; Cordaillat, Magali; Carretero, Oscar A et al. (2012) Histone acetyl transferases CBP and p300 are necessary for maintenance of renin cell identity and transformation of smooth muscle cells to the renin phenotype. Am J Physiol Heart Circ Physiol 302:H2545-52
Medrano, Silvia; Monteagudo, Maria C; Sequeira-Lopez, Maria Luisa S et al. (2012) Two microRNAs, miR-330 and miR-125b-5p, mark the juxtaglomerular cell and balance its smooth muscle phenotype. Am J Physiol Renal Physiol 302:F29-37
Kurt, Birguel; Kurtz, Lisa; Sequeira-Lopez, Maria L et al. (2011) Reciprocal expression of connexin 40 and 45 during phenotypical changes in renin-secreting cells. Am J Physiol Renal Physiol 300:F743-8
Xu, Di; Borges, Giulianna R; Davis, Deborah R et al. (2011) Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism. Physiol Genomics 43:286-94
Castellanos Rivera, Ruth M; Monteagudo, Maria C; Pentz, Ellen S et al. (2011) Transcriptional regulator RBP-J regulates the number and plasticity of renin cells. Physiol Genomics 43:1021-8
Brunskill, Eric W; Sequeira-Lopez, Maria Luisa S; Pentz, Ellen S et al. (2011) Genes that confer the identity of the renin cell. J Am Soc Nephrol 22:2213-25
Sequeira Lopez, Maria Luisa S; Gomez, R Ariel (2011) Development of the renal arterioles. J Am Soc Nephrol 22:2156-65
Desch, Michael; Schreiber, Andrea; Schweda, Frank et al. (2010) Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells. Hypertension 55:660-6
Wagner, Charlotte; Jobs, Alexander; Schweda, Frank et al. (2010) Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension. Kidney Int 78:762-8

Showing the most recent 10 out of 18 publications